Differential IL-4/Stat6 activities correlate with differential expression of regulatory genes SOCS-1, SHP-1, and PP2A in colon cancer cells

J Cancer Res Clin Oncol. 2009 Jan;135(1):131-40. doi: 10.1007/s00432-008-0429-8. Epub 2008 Jun 7.

Abstract

Purpose: To investigate potential differences in the expression of Stat6 regulatory genes that may influence IL-4/Stat6 activities (phenotypes) in colon cancer cells.

Methods: RT-PCR method was employed to examine the constitutive mRNA expression of Stat6 negative regulators SOCS-1 and SHP-1, and positive regulator PP2A in colon cancer cell lines HT-29 and Caco-2. Stat6 protein expression and nuclear phosphorylation were detected using Western blotting.

Results: Caco-2 cells carrying inactive Stat6(null) phenotype showed normal constitutive expression of Stat6 but decreased phosphorylation of nuclear Stat6 compared with HT-29 cells carrying active Stat6(high) phenotype. Stat6(null) Caco-2 cells expressed increased levels of mRNA and protein of SOCS-1 and SHP-1, and decreased mRNA expression of PPP2CA and PPP2CB, encoding two critical subunits of PP2A.

Conclusions: Constitutively increased expression of Stat6 negative regulators SOCS-1 and SHP-1, together with decreased expression of positive regulator PP2A, may play a role in forming the inactive Stat6(null) phenotype in colon cancer cells.

MeSH terms

  • Blotting, Western
  • Cell Nucleus / metabolism
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • Cytoplasm / metabolism
  • Humans
  • Interleukin-4 / genetics*
  • Interleukin-4 / metabolism
  • Phenotype
  • Phosphorylation
  • Protein Phosphatase 2 / genetics*
  • Protein Phosphatase 2 / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT6 Transcription Factor / genetics*
  • STAT6 Transcription Factor / metabolism
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics*
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Tumor Cells, Cultured

Substances

  • IL4 protein, human
  • RNA, Messenger
  • SOCS1 protein, human
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Interleukin-4
  • PPP2CA protein, human
  • PPP2CB protein, human
  • Protein Phosphatase 2
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6